Polymer-Based Reconstruction of the Inferior Vena Cava in Rat: Stem Cells or RGD Peptide?

Abstract

As part of a program targeted at developing a resorbable valved tube for replacement of the right ventricular outflow tract, we compared three biopolymers (polyurethane [PU], polyhydroxyalkanoate (the poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-4-hydroxyvalerate) [PHBVV]), and polydioxanone [PDO]) and two biofunctionalization techniques (using adipose-derived stem cells [ADSCs] or the arginine-glycine-aspartate [RGD] peptide) in a rat model of partial inferior vena cava (IVC) replacement. Fifty-three Wistar rats first underwent partial replacement of the IVC with an acellular electrospun PDO, PU, or PHBVV patch, and 31 nude rats subsequently underwent the same procedure using a PDO patch biofunctionalized either by ADSC or RGD. Results were assessed both in vitro (proliferation and survival of ADSC seeded onto the different materials) and in vivo by magnetic resonance imaging ( MRI), histology, immunohistochemistry [against markers of vascular cells (von Willebrand factor [vWF], smooth muscle actin [SMA]), and macrophages ([ED1 and ED2] immunostaining)], and enzyme-linked immunosorbent assay (ELISA; for the expression of various cytokines and inducible NO synthase). PDO showed the best in vitro properties. Six weeks after implantation, MRI did not detect significant luminal changes in any group. All biopolymers were evenly lined by vWF-positive cells, but only PDO and PHBVV showed a continuous layer of SMA-positive cells at 3 months. PU patches resulted in a marked granulomatous inflammatory reaction. The ADSC and RGD biofunctionalization yielded similar outcomes. These data confirm the good biocompatibility of PDO and support the concept that appropriately peptide-functionalized polymers may be successfully substituted for cell-loaded materials.

A comparative evaluation of the effect of polymer chemistry and fiber orientation on mesenchymal stem cell differentiation

“…Studies of in vitro MSC differentiation on electrospun PDO are limited. Electrospun PDO scaffolds have shown to facilitate growth of human dental pulp stem cells and differentiation of adipose‐derived stem cells down adipogenic and chondrogenic cell lines in vitro . In vivo studies have shown that electrospun PDO scaffolds facilitate the differentiation of MSCs into vascular tissue …”

RGD constructs with physical anchor groups as polymer co‐electrospinnable cell adhesives

“…Figure depicts electron microscopy pictures of the electrospun non‐wovens mats. In all cases, the co‐electrospinning proceeded well, and the fiber orientation, fiber diameter and porosity (see Table ) were comparable for all investigated samples and are very similar to pure electrospun PPDO …”

“…PPDO patches co‐electrospun with unmodified (free) RGD (Ac‐Gly‐Arg‐Cys‐Gly‐Arg‐Gly‐Asp‐Ser‐Pro‐Gly‐NH 2 ) were prepared as previously reported …”

“…Aliphatic polyesters, which are widely applied in temporary implants, lack functional groups allowing covalent coupling of peptides. An interesting option to realize RGD presentation on a polymer fiber is its physical incorporation by co‐electrospinning . Leaking of RGD as soluble RGD may, however, inhibit cell adhesion and might promote apoptosis …”

Fibers for hearts: A critical review on electrospinning for cardiac tissue engineering

“…The PDO electrospun tissue-engineered valved transannular patch appears to be a promising device in restoring a living RVOT and could ultimately lead to applications in the treatment of congenital RVOT diseases. The same group further compared electrospun scaffolds of PU, poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-4-hydroxyvalerate (PHBVV) and PDO, using two biofunctionalization techniques: adipose-derived stem cells or arginine-glycine-aspartate (RGD) peptide in a rat model of partial inferior vena cava replacement [117]. In vitro studies using adipose-derived stem cells and in vivo results revealed the superior properties of PDO, while the two functionalization methods yielded similar outcomes.…”